Gene discovery clarifies misunderstood disease

U. PITTSBURGH (US)—A genetic mutation for inherited lymphedema associated with lymphatic function has been discovered that could help create new treatments for the condition.

Lymphedema, the swelling of body tissues caused by an accumulation of fluid in a blocked or damaged lymphatic system, affects more than 120 million people worldwide. The most common treatments are a combination of massage, compression garments, or bandaging.

“Lymphedema was first described hundreds of years ago, and yet it remains a very poorly understood disease,” says David Finegold, professor of human genetics at the University of Pittsburgh and co-principal investigator of the new study.

“Unfortunately, there is no drug available to cure or even treat it. Most people with inherited lymphedema suffer their entire lives with treatments that address symptom relief only.”

The study, published in the June issue of the American Journal of Human Genetics,is based on the University of Pittsburgh Lymphedema Family Study, which began collecting data from affected families in 1995 to learn more about the risk factors and causes of inherited, or primary, lymphedema.

Previous research has helped identify six genes linked to the development of lymphedema, but until now researchers had no insight into the genetic factors responsible for lymphatic vascular abnormalities.

Finegold sequenced three genes expressed in families with primary lymphedema. Mutations in one of these genes, GJC2, was found in primary lymphedema families and are likely to impair the ability of cells to push fluid throughout the lymphatic system by interrupting their signaling.

Without proper signaling, cell contraction necessary for the movement of fluid did not occur, leading to its accumulation in soft body tissues.

“These results are significant because they give us insight into the cell mechanics that may underlie this condition,” says Finegold. “With further research, we may be able to target this gene with drugs and improve its function.”